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Introduction: In patients with intracerebral hemorrhage (ICH) perihemorrhagic edema (PHE) seems to play a predictive role besides initial hematoma size, clinical status and intraventricular bleeding (IVH). PHE may exceed the initial hematoma volume by up to 600% thereby leading to increased intracranial pressure (ICP) which may cause severe clinical deterioration. EUSI and ASA guidelines recommend the use of intravenous mannitol or hypertonic saline (HS) in order to reduce elevated ICP. However, clinical data suggest that HS may be superior to mannitol in lowering ICP and clinical data concerning the effect of mannitol on PHE as a cause of elevated ICP is limited. We aimed to investigate the effect of mannitol on PHE after ICH.Methods: Patients with supratentorial spontaneous ICH treated with 20% intravenous mannitol solution (125-250ml every 6h) for 5-10 days and controls matched for ICH volume, age and IVH who did not receive any osmotic agents during the course of treatment were identified retrospectively from our institutional ICH database. PHE volume was calculated on diagnostic CT scans performed on days 1, 2-3, 4-6, 7-9 and 10-12 using a validated volumetric algorithm. Frequency of elevated ICP up to day 12 (ICP burden), modified Rankin Scale (mRS) after rehabilitation (approx. day 90) and PHE evolution were assessed as outcome variables.Results: 44 ICH patients treated with mannitol and 43 controls were included. Basic characteristics did not differ between groups (median ICH volume day 1: 32.9 mL (IQR 16.3 - 54.0) and 27.7 mL (IQR 22.4 - 37.1), p=0.786; median age 71 y (IQR 61.5 - 77) and 72 y (IQR 66 - 81), p=0.269; median PHE volume day 1: 24.3 mL (IQR 16.0 - 38.8) and 24.3 mL (IQR 17.1 - 32.1), p=0.592, respectively). In the mannitol group PHE volume exceeded to a greater extent than in controls (PHE on day 10-12: 60.1 mL (SD 33.6) vs. 36.8 mL (SD 23.2), p=0.005). Median ICP burden was higher in the mannitol group (0 (IQR 0 - 7.75) vs. 0 (IQR 0), p=0.016). Median mRS did not differ between both groups (4 (IQR 4-6) vs. 4 (IQR 3-6), p=0.321).Conclusions: We found no effect of mannitol use on the general evolution of PHE and ICP. Other underlying mechanisms may explain the short-term effect of mannitol bolus administration on ICP in patients with spontaneous supratentorial ICH.